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Combining substances and multi-day sequences: what has been reported

The question here is what is documented about taking more than one substance in a session or retreat, together or on consecutive days. This card sets out what trials, surveys, case reports and interviews with retreat organizations report.

Published Information current to 7 November 2026Review due by 5 February 2027

Read this first. This page is education, not instructions to use. Metanoia does not supply any substance. In the United States, most of the substances discussed here are Schedule I under federal law (21 CFR 1308.11). State programs such as Oregon's and Colorado's operate under state law only, and federal law still applies. Legal status differs between countries, and none of this is legal advice. Nothing here is medical advice, and nothing here gives or recommends a dose. People who host, supply or take part in sessions involving controlled substances can face criminal liability under federal and state law. This page does not advise on that. “Healthy adults” means people with no diagnosed psychiatric or major medical condition, the population Metanoia studies. This page reports what published sources say about work done outside supervised programs, and it takes no position on the legality of any setting, practice or person.
Not an emergency resource. Metanoia is not an emergency service. In a medical or mental health emergency in the United States the number is 911, and the 988 Suicide and Crisis Lifeline is available by call or text. Elsewhere, local emergency numbers apply. Nothing on this card is a reason to delay or avoid care. This card describes what sources report. It is not a screening tool, it does not say who should take part in a session or in what setting, and it is not medical guidance.

The short answer

What is documented about taking more than one substance in a session or retreat, together or on consecutive days?

Two trials read in full tested a combination in a laboratory: MDMA with LSD in 24 healthy adults, and a harmine and DMT formulation in healthy men. Nothing read in full tested a planned sequence of different substances over days. The rest is surveys, online reports, case reports, a review and an interview study of retreats. They describe what is done and what went wrong without measuring either reliably. This card does not say what anyone should do.

What do studies report?

Reported findings, not recommendations. This marking applies to everything in this section. Each finding applies only to the group named, and an association is not a cause.

Combinations tested in trials and surveys

  • Swiss crossover trial, 2023. In 24 healthy adults, MDMA and LSD taken together in a laboratory did not change the quality of the subjective effects compared with LSD alone, and the effects lasted about 1.5 hours longer. Blood pressure and heart rate rose more, and LSD blood levels fell more slowly. The authors report no severe adverse events. One dose of each substance and one timing were tested. Source 1, level 1
  • Online survey, 2023. Of 698 people planning to use psilocybin or LSD, 27 also took MDMA. Those who called their MDMA dose low reported less grief and fear and more self-compassion, love and gratitude, and medium-to-high doses showed no difference. Doses were self-labeled, groups were small, and the authors warn that no difference is not proof of no effect. Source 2, level 1
  • Harmine then DMT in healthy men. In a laboratory trial of 31 healthy men, a harmine and DMT formulation produced DMT effects for roughly 2 to 3 hours, and harmine alone resembled placebo. Nausea was reported by 9 men, a fast pulse by 12 and physical distress by 14, all passing in that study, and blood pressure rose. DMT alone was not tested. Source 3, level 1

Reports of problems and of what retreats offer

  • Online reports with lithium, 2021. An analysis of 96 reports posted on public websites by people who took a classic psychedelic with a mood stabilizer found that 29 of 62 lithium reports (47%) described seizures, and 39% described medical attention. None of 34 lamotrigine reports described a seizure. In 18 of the lithium reports another active substance was also involved. The reports were self-selected and unverified, and most gave no dose. The authors call the data low quality and provisionally conclude that psychedelic use may pose a significant seizure risk for patients on lithium. This card does not address starting, continuing or stopping any medicine. Source 4, level 1
  • Systematic review, 2024. The review describes two case reports of serious events after 5-MeO-DMT taken with harmala-containing plant material or an herbal preparation, one severe reaction and one death. It states that the cause of the toxicity remains unclear and that both reports were criticized. The original reports were not read. Source 5, level 1
  • Case report, 2026. One report describes a 46-year-old man with serotonin syndrome and respiratory failure, then full recovery, after ayahuasca on three days and then products containing dextromethorphan and diphenhydramine. Exposure was by the patient's account, with no toxicology. Source 6, level 1
  • Interviews with retreat organizations, 2023. Of 49 organizations interviewed, 19 offered more than one psychedelic and 15 offered both a psychedelic and a non-psychedelic substance such as kambo, sananga or cannabis. One example was ayahuasca on four days and San Pedro on two. Organizations reported on themselves, and the authors say closely spaced combinations remain understudied. Source 7, level 1

What is not known?

“Not located” means that the searches Metanoia ran on 7 November 2026 did not return it. They covered PubMed, ClinicalTrials.gov and the Europe PMC preprint index. Embase, PsycINFO, Web of Science, Google Scholar, harm-reduction charts and forums were not searched. Papers seen in abstract only were not used, among them a 2026 review of MAO inhibitors.

  • Whether MDMA one day and psilocybin the next, or any day-to-day order, changes anything. A Basel trial in 24 healthy adults that tests MDMA given together with psilocybin is registered as completed on 28 May 2026. The record posted no results at its last update on 25 June 2026, and no paper turned up by 7 November 2026 (source 8, level 1). This is a registry fact, and the trial gave the two together, not on separate days.
  • How tolerance carries from one substance to the next day. No modern human study was located in full text, and older experiments were not available in full.
  • Tramadol with a classic psychedelic. One PubMed search returned no report of this, and the 2024 review above does not mention tramadol.
  • A “preparation ladder” of different substances. No study or registry record under that name or similar terms was found in PubMed, Europe PMC or ClinicalTrials.gov.

What this card does not say

  • It does not say whether anyone should combine, avoid or sequence substances. It is not a standard of care. A figure from a studied group is not a statement about any person.
  • Nothing here concerns starting, continuing or stopping any medicine. Medicines are on the cards about ayahuasca and antidepressants, antidepressants and other psychiatric medicines and heart and blood pressure. Everyday substances, amounts and repeated sessions are separate entries, not yet written.
  • This is not an emergency resource. In the United States, 911 and the 988 line are available.
  • It does not rate how risky, safe or worthwhile any combination is.

Send a correction

If this card reports something wrongly, tell us. Write to main@metanoia-ca.org and keep the card name in the subject line. Accounts of what happened in a session belong in the field reports channel, not in email. Please leave out names and anything that identifies a person or a place. We read every message.

Where does this come from?

Grade key: 1 = peer-reviewed publication or official document. A grade names the type of source, and the design and limits are given in the text. “Read in full” means Metanoia read every sentence on the date given, and any part not read is named.

Review due by 5 February 2027.

  1. Straumann I, Ley L, Holze F, Becker AM, Klaiber A, Wey K, Duthaler U, Varghese N, Eckert A, Liechti ME. Acute effects of MDMA and LSD co-administration in a double-blind placebo-controlled study in healthy participants. Neuropsychopharmacology 2023. DOI 10.1038/s41386-023-01609-0 PMID 37258715. Grade 1. Randomized crossover trial. Text and tables read in full 7 November 2026 (figures and supplement not read).
  2. Zeifman RJ, Kettner H, Pagni BA, Mallard A, Roberts DE, Erritzoe D, Ross S, Carhart-Harris RL. Co-use of MDMA with psilocybin/LSD may buffer against challenging experiences and enhance positive experiences. Sci Rep 2023. DOI 10.1038/s41598-023-40856-5 PMID 37608057. Grade 1. Prospective online survey, convenience sample. Text read in full 7 November 2026 (figures and supplement not read).
  3. Mueller MJ, Aicher HD, Dornbierer DA, et al. Pharmacokinetics and pharmacodynamics of an innovative psychedelic N,N-dimethyltryptamine/harmine formulation in healthy participants: a randomized controlled trial. Int J Neuropsychopharmacol 2025. DOI 10.1093/ijnp/pyaf001 PMID 39774840. Grade 1. Randomized crossover trial in healthy men, with tasks during sessions. Text read in full 7 November 2026 (figures and supplement not read).
  4. Nayak SM, Gukasyan N, Barrett FS, Erowid E, Erowid F, Griffiths RR. Classic psychedelic coadministration with lithium, but not lamotrigine, is associated with seizures: an analysis of online psychedelic experience reports. Pharmacopsychiatry 2021. DOI 10.1055/a-1524-2794 PMID 34348413. Grade 1. Peer-reviewed analysis of forum reports. Text read in full 7 November 2026 (figures and supplement not read). Two authors work for Erowid, one of the websites searched. The wording of the conclusion was checked against the abstract on the same date.
  5. Halman A, Kong G, Sarris J, Perkins D. Drug-drug interactions involving classic psychedelics: a systematic review. J Psychopharmacol 2024. DOI 10.1177/02698811231211219 PMID 37982394. Grade 1. Systematic review, so the studies it covers were not read. Text read in full 7 November 2026 (supplement not read). Statements about the original case reports are as the review gives them.
  6. Pack S, Ellett TR, Pham J, et al. Severe serotonin syndrome with acute respiratory failure following ayahuasca and dextromethorphan use: a case report. Cureus 2026. DOI 10.7759/cureus.114211 PMID 42713547. Grade 1. Single case report. Text read in full 7 November 2026 (figures not read).
  7. McGuire AL, Neitzke-Spruill L, Robinson JO, et al. Reported safety practices of publicly advertised psychedelic retreats. JAMA Netw Open 2026. DOI 10.1001/jamanetworkopen.2025.52505 PMID 41499117. Grade 1. Qualitative interview study, organizations reporting on themselves, 61.7% response. Text read in full 7 November 2026 (supplement not read). Some percentages in the paper disagree between text and table, so this card uses counts only.
  8. ClinicalTrials.gov, NCT06884514, Acute Effects of MDMA Co-administration on the Response to Psilocybin in Healthy Subjects, University Hospital Basel. Grade 1. Registry record, last update posted 25 June 2026. Read in full 7 November 2026, no results section.